We have demonstrated that low-dose, whole-body irradiation and extracorporeal immunosorption to remove circulating immune complexes (CIC) and IgG resulted in complete regression of feline lymphosarcoma (LSA) and a reversal of feline leukemia virus (FeLV) infection. In this proposal, we will attempt to improve the ex vivo immunosorption therapy and study the possible mechanisms by which anti-viral and anti-tumor responses occur. In order to improve the effectiveness of immunosorption as a therapy, we will remove CIC that contain IgG using Staph. aureus Cowan I or protein A bound to a solid matrix by passing plasma from FeLV-infected, LSA-bearing cats over columns prepared with these two immunosorbents. Treated plasma will then be returned to the host. Protein A, which is on the surface of S. aureus, binds non-specifically to the Fc portion, thus it will be used as the immunosorbent. Different therapeutic protocols will be used to determine the effectiveness of whole-body irradiation alone, ex vivo immunosorbent alone or the two combined, for the treatment of LSA and FeLV. The most effective protocol will then be studied in detail. To better understand the mechanism of the anti-FeLV and anti-tumor response, the results of immunosorption on the humoral immunity will be studied. The serum levels of FeLV antigens, FeLV antibody, FOCMA and FOCMA antibody will be monitored during the course of treatments. Complement and CIC levels will be determined regularly to detect changes in these parameters during therapy. We will study the biochemical nature of the molecules removed from the plasma of treated animals by appropriate anti-sera and column chromatographic separation. These studies may result in the development of a therapy for LSA and in a better understanding of the mechanism by which a retroviral infected, tumor-bearing host develops its disease.